Preventing Heart Problems While Keeping a Cool Head

Preventing Heart Problems While Keeping a Cool Head

The reason for this is that treatment with nicotinic acid has an unpleasant but harmless side-effect: the drug makes patients turn quite red in the face. Scientists at the Max Planck Institute for Heart and Lung Research have now discovered the mechanism behind this effect, which is known as flushing. This will enable the development of flush inhibitors.

The treatment of lipid metabolic disorders is one of the important measures used in the prevention of cardio-vascular disease. Cholesterol is the key molecule here and LDL cholesterol is the type of cholesterol most widely discussed in this context. This "bad" cholesterol is one of the most important risk factors for the emergence of cardio-vascular diseases. The higher the blood-plasma concentration of LDL cholesterol, the higher an individual's risk of suffering cardiac arrest or peripheral vascular disease. The opposite applies to the "good" HDL cholesterol: the higher the level of HDL cholesterol, the lower the risk of contracting these diseases. For this reason, the strategy of increasing HDL plasma concentration through medication has become more prevalent of late.

"The main problem with treatment using nicotinic acid – which has nothing to do with the nicotine in tobacco, by the way – is flushing," says Stefan Offermanns, Director of the Department of Pharmacology at the Max Planck Institute. "Just a short time after taking nicotinic acid, the patient experiences strong flushing of the face and upper body for up to one and a half hours. This is caused by the dilation of blood vessels in the skin." The flushing symptoms are completely harmless. However, patients often abandon the treatment on account of these symptoms.

Offermanns and his colleagues had already succeeded in identifying a specific receptor for nicotinic acid that conveys the desired effects of nicotinic acid. Tests on mice showed, however, that the receptor is also responsible for the nicotinic-acid-induced flushing reaction. "We have now succeeded in demonstrating that the receptor exists both in the main cells of the top layer of the skin or epidermis, which are called keratinocytes, and the immune cells, known as Langerhans cells, also found in the epidermis," reports Offermanns.

By studying mouse strains in which the receptor in either the Langerhans cells or keratinocytes is blocked, the researchers were able to show that the first phase of the flushing reaction is triggered by the activation of Langerhans cells. In contrast, the second and longer phase results from the activation of the keratinocytes. In both phases, different prostaglandins are formed. "The flushing phenomenon can be prevented by inhibiting prostaglandin formation or blocking the prostaglandin receptors in the skin, while the desired effects of the nicotinic acid on lipid metabolism remain unaffected."